What precautions and monitoring are necessary when initiating tofacitinib (Janus kinase inhibitor) therapy?

Precautions and Monitoring When Starting Tofacitinib Therapy

Before initiating tofacitinib therapy, comprehensive screening for infections and baseline laboratory testing must be performed, followed by regular monitoring of blood counts, liver function, and lipid levels to minimize serious adverse events including infections, thrombosis, and malignancy.

Pre-Treatment Screening and Baseline Testing

Infection Screening

• Tuberculosis (TB) screening is conditionally recommended prior to starting tofacitinib 1
  • Perform interferon-gamma release assay or tuberculin skin test
  • Chest X-ray
• Viral screening:
  • Hepatitis B and C serology
  • HIV testing (if risk factors present)
  • Consider varicella zoster virus (VZV) serology if no history of chickenpox, shingles, or vaccination 2

Baseline Laboratory Tests

• Complete blood count (CBC) with differential 1, 2
• Liver function tests (LFTs) 1, 2
• Lipid profile 1, 2
• Renal function tests

Vaccination Considerations

• Complete any needed live vaccines before initiating tofacitinib 1, 2
• Consider recombinant zoster vaccine (Shingrix) before starting therapy, especially in older patients 2
  • This is particularly important as JAK inhibitors increase the risk of herpes zoster reactivation

Monitoring Schedule During Treatment

First 1-2 Months

• CBC with differential 1, 2
• LFTs 1, 2
• Lipid profile (1-2 months after starting) 1, 2, 3

Ongoing Monitoring

• CBC and LFTs every 3-4 months 1, 2
• Annual lipid profile 2
• Annual TB screening if in high-risk area 1
• Monitor for signs of infection, particularly herpes zoster 2

Laboratory Abnormalities Requiring Dose Adjustment or Discontinuation

Hematologic Parameters

• Discontinue tofacitinib if:
  • Hemoglobin <8 g/dL or decreases >2 g/dL 1, 2, 3
  • Absolute neutrophil count (ANC) <500/mm³ 1, 2, 3
  • Absolute lymphocyte count <500/mm³ 1, 2, 3
• Interrupt dosing if:
  • ANC 500-1000/mm³ until ANC ≥1000/mm³ 3

Liver Function

• Do not initiate if LFTs >1.5 times upper limit of normal (ULN) 3
• Interrupt dosing if LFTs >3 times ULN 3
• Discontinue if LFTs >5 times ULN 3
• Consider drug-induced liver injury if significant elevations occur 3

Special Precautions and Warnings

Cardiovascular Risk

• FDA has issued a black box warning for increased risk of serious heart-related events, cancer, blood clots, and death 1
• Use with caution in patients with cardiovascular risk factors 1
• Particularly cautious use in acute severe conditions like acute severe ulcerative colitis, which is itself a risk factor for thrombosis 1

Infection Risk

• Monitor for signs of serious and opportunistic infections 1, 2
• Particular vigilance for:
  • Tuberculosis (including disseminated disease)
  • Herpes zoster (shingles)
  • Bacterial, fungal, and viral infections
  • Common serious infections: cellulitis, urinary tract infection, pneumonia 1

Malignancy Risk

• Increased risk of malignancies, including lymphoma 1
• Most common nonhematologic malignancies: lung and breast cancer 1
• Epstein-Barr virus-associated post-transplant lymphoproliferative disorder has been reported in patients receiving concurrent immunosuppressive medications 1

Dose Considerations

• The recommended dose varies by indication
• Consider lower doses in patients with renal dysfunction 2
• For maintenance therapy in conditions like ulcerative colitis, use the lowest effective dose to minimize adverse events 4

Common Pitfalls and Caveats

1. Failure to screen for latent TB - Always screen before starting therapy
2. Inadequate monitoring - Adherence to monitoring schedule is crucial
3. Missing early signs of infection - Educate patients about infection symptoms
4. Ignoring cardiovascular risk factors - Assess and manage these before starting therapy
5. Continuing treatment despite significant laboratory abnormalities - Follow discontinuation criteria strictly
6. Not considering drug interactions - Review all concurrent medications

By following these comprehensive precautions and monitoring protocols, the risk of serious adverse events with tofacitinib therapy can be minimized while maintaining treatment efficacy.